Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes

The study analyzed rare coding genetic variants in 397,065 UK Biobank participants with whole-exome sequencing across 36 sleep phenotypes including self-reported data, diagnoses, sleep medication use, and accelerometry. Results were meta-analyzed with 171,536 participants from the All of Us project of diverse ancestries and replicated in the Mass General Brigham Biobank (31,275 participants). The research identified 260 genes associated with sleep phenotypes, including 29 novel genes linked to sleep medication use, of which 24 had not been previously reported in connection with sleep phenotypes. Significant genetic correlations were found between sleep medication use, insomnia, and fatigue. Gene expression trajectory analyses showed that genes associated with self-reported sleep traits have constant high expression during the prenatal period, while genes linked to sleep medication phenotypes show peak expression in the late prenatal period.